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Abstract Introduction There are a growing number of surgical approaches for laparoscopic radical resection of right-sided colon cancer, while there are relatively few comparative analyses of the different surgical approaches. Objective To evaluate the safety and efficacy of different surgical approaches (intermediate approach, caudolateral approach, caudolateral combined with intermediate approach) for laparoscopic radical resection of right-sided colon cancer by conducting a network meta-analysis (NMA). Method We searched PubMed, Web of science and China National Knowledge Infrastructure (CNKI) databases. We reviewed the Chinese and English literature on controlled studies of laparoscopic radical resection of right-sided colon cancer including intermediate approach, caudolateral approach and caudolateral combined with intermediate approach, reported from the establishment of the database to September 2023. The inclusion and exclusion criteria were independently conducted by two researchers and relevant data was extracted from the qualifying literature and analyzed using Stata15 software. Results Nine controlled studies of relevance including 715 patients were screened with right-sided colon cancer. Net meta-analysis showed that compared with the intermediate approach, the caudolateral approach was superior to the intermediate approach in terms of operation time (SMD = 0.75, 95% CI = 0.38 ~ 1.12, P = 0.0001), and bleeding volume (SMD = 1.15, 95% CI = 0.18 ~ 2.13, P = 0.002), while the difference was not statistically significant among the caudolateral approach compared with the intermediate approach in terms of the number of lymph node dissection, postoperative complication rate, time to first postoperative flatus and postoperative hospitalization. Compared with the intermediate approach, the combined approach was superior to the intermediate approach in terms of operation time (SMD = -0.87, 95% CI = -1.22 ~ -1.52, P

Abstract The uncertainty regarding the correlation between sea spray aerosol (SSA) formation and sea surface temperature (SST) hinders the accurate estimation of SSA’s impact on global climate. Here, we developed a temperature-controlled plunging SSA simulation tank to investigate the impact of SST on SSA formation from two perspectives: SSA particle size distribution and organic enrichment. Our findings show that SSA particle size decreases with decreasing SST, as exhibited by an increase in SSA within Aitken mode and a decrease in SSA within accumulation and coarse modes. SST can significantly enhance organic enrichment in SSA particles, while the multiplicative increases vary from 2 to 10 times depending on the organic matter species and the SSA particle size. Based on our experimental results, it is predicted that SST reduction may lead to a significantly higher contribution of Aitken modal SSA-derived CCN in cold waters (0 °C) than in warm waters (30 °C). Additionally, we incorporate SST for the first time in estimating the global flux of dissolved organic carbon (DOC) emitted via SSA, yielding a value ranging from 23.45 to 55.78 Tg C yr−1. Compared to previous works, our study reveals the crucial role of SST in influencing both cloud formation and the atmospheric organic burden of SSA.

Abstract Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants.

Abstract Background The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency. Results In this study, we synthesized 623 alkyne-bearing ionizable lipids using the A3 coupling reaction and assessed their effectiveness in mRNA delivery. ILs with specific structural features—18-carbon alkyl chains, a cis-double bond, and ethanolamine head groups—demonstrated superior mRNA delivery capabilities. Variations in saturation, double bond placement, and chain length correlated with decreased efficacy. Alkynes positioned adjacent to nitrogen atoms in ILs reduced the acid dissociation constant (pKa) of LNPs, thereby hindering mRNA delivery efficiency. Conversion of alkynes to alkanes significantly enhanced mRNA delivery of ILs both in vitro and in vivo. Moreover, combining optimized ILs with cKK-E12 yields synergistic LNPs that showed markedly augmented mRNA expression levels in vivo. Conclusions Overall, our study provides insights into the structure–function relationships of ILs, providing a foundation for the rational design of ILs to enhance the efficacy of LNPs in mRNA delivery. Graphical Abstract

Abstract Background The integration of 7 Tesla (7T) magnetic resonance imaging (MRI) with advanced multimodal artificial intelligence (AI) models represents a promising frontier in neuroimaging. The superior spatial resolution of 7TMRI provides detailed visualizations of brain structure, which are crucial forunderstanding complex central nervous system diseases and tumors. Concurrently, the application of multimodal AI to medical images enables interactive imaging‐based diagnostic conversation. Methods In this paper, we systematically investigate the capacity and feasibility of applying the existing advanced multimodal AI model ChatGPT‐4V to 7T MRI under the context of brain tumors. First, we test whether ChatGPT‐4V has knowledge about 7T MRI, and whether it can differentiate 7T MRI from 3T MRI. In addition, we explore whether ChatGPT‐4V can recognize different 7T MRI modalities and whether it can correctly offer diagnosis of tumors based on single or multiple modality 7T MRI. Results ChatGPT‐4V exhibited accuracy of 84.4% in 3T‐vs‐7T differentiation and accuracy of 78.9% in 7T modality recognition. Meanwhile, in a human evaluation with three clinical experts, ChatGPT obtained average scores of 9.27/20 in single modality‐based diagnosis and 21.25/25 in multiple modality‐based diagnosis. Our study indicates that single‐modality diagnosis and the interpretability of diagnostic decisions in clinical practice should be enhanced when ChatGPT‐4V is applied to 7T data. Conclusions In general, our analysis suggests that such integration has promise as a tool to improve the workflow of diagnostics in neurology, with a potentially transformative impact in the fields of medical image analysis and patient management.

Abstract Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association.

Abstract The leafminer Liriomyza trifolii causes severe economic damage on ornamental and horticultural crops in China. Rapid cold hardening (RCH) is a phenomenon where cold tolerance in insects can be significantly enhanced after a short-term acclimation to low temperatures. In this study, the regulation of transcription in response to cold hardening was investigated in L. trifolii adults, and fatty acids and cryoprotectant levels were measured. The composition of fatty acids changed after RCH treatment, and glucose and trehalose levels showed significant accumulation after acclimation, thus indicating that changes in fatty acids and cryoprotectants contribute to RCH in L. trifolii. RNA-seq was used to analyze transcriptional regulation after a 4 h hardening period and showed that differentially expressed genes clustered in multiple metabolic pathways, which indicates the importance of transcriptional regulation in RCH. This study expands our knowledge of biochemical and transcriptional changes in L. trifolii during cold hardening and provides a basis for further investigations aimed at understanding thermal adaptation in insects.

Abstract Background Previous research has indicated that personality traits, loneliness, and problematic internet use (PIU) significantly contribute to the prevalence of adolescent depression. However, the specific interrelationships among these variables in explaining the occurrence of depression remain unclear. Drawing upon susceptibility theory and cognitive-behavioral theory, this study explored whether personality traits influences adolescent depression through loneliness and PIU. Methods A total of 2476 adolescents (aged 12–18) from all over the country completed a psycho-social test, including the 10-Item Big Five Personality Inventory (BFI-10), three-Item Loneliness Scale (T-ILS), Problematic Internet Use Questionnaire-Short Form (PIUQ-SF-6) and the Patient Health Questionnaire-9 (PHQ-9). The mediation model was built and bootstrap method was used to test the mediating effect. Results Results showed that neuroticism, conscientiousness, openness, and agreeableness have a direct role on depression. Loneliness and PIU partially mediated the relationship between neuroticism, conscientiousness, agreeableness and depression, and completely mediated the relationship between extroversion and depression. Conclusions The results suggest that loneliness and PIU play important mediating roles in the relationship between personality traits and depression. This remind us that alleviating sense of loneliness and reducing overuse of the internet are a strategy for improve depression among adolescents.

Abstract Background As the emergence of technologies such as sequencing and gene mapping, significant advancements have been made in understanding the landscape of tumors. However, the effective treatment of tumors continues to pose a tremendous challenge in clinical practice, which highlights the importance of predicting tumor markers and studying drug resistance mechanisms. The prognosis and differential expression of STARD7 in human pan-cancer were investigated by bioinformatic methods and experimental verification. Methods The expression, diagnostic, and prognostic significance of the STARD7 gene were comprehensive analyzed using bioinformatics techniques. Furthermore, we validated our projected outcomes in liver cancer through experimental methodologies, including the use of qRT-PCR, CCK8 and transwell assays. Results The STARD7 gene exhibits differential expression in 25 tumors, with high expression observed in 22 tumors. These distinct expression patterns within different tumor types are closely associated with poor prognosis and diagnosis. Furthermore, the STARD7 gene plays a role in regulating the tumor immune microenvironment. Methylation levels of STARD7 vary among 20 types of tumors and are correlated with survival outcomes. Furthermore, the experiment results demonstrated that STARD7 is highly expressed in hepatocellular carcinoma cells. Suppression of STARD7 significantly impedes the proliferation, migration, and invasion of HepG-2 and SMMC-7721 cells. Conclusions STARD7 has the potential to function as a crucial prognostic biomarker and exhibit correlation with tumor immunity in various types of human cancers. The implications of our findings extend to informing cancer immune-therapy and promoting the advancement of precision immune-oncology.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa−1, as well as cyclic stability (over 500 cycles), a wide detection range of 0–150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

Abstract Background In recent years, there has been a significant decrease in the desire to have children among Chinese women of childbearing age, particularly for the first child. This trend has sparked a growing interest in understanding the underlying factors. Although perceived stress has been speculated as an important factor in decreasing fertility intention, the precise mechanism is unclear. The current study, therefore, aims to investigate the psychological mechanisms linking perceived stress to fertility intentions among women of childbearing age without children, a topic of significant relevance and importance. Methods Data were sourced from Chinese residents' psychology and behavior investigation (PBICR-2022). A multistage random sampling method was applied to recruit eligible participants. The Mplus8.3 software constructed a chain path model among the variables. Results The median fertility intention was 30(3–60) on a scale of 0 to 100. The mediation analysis revealed a significant negative influence of perceived stress on fertility intention (β = − 0.076, P

With the advent of the era of big data, an increasing amount of duplicate data are expressed in different forms. In order to reduce redundant data storage and improve data quality, data deduplication technology has never become more significant than nowadays. It is usually necessary to connect multiple data tables and identify different records pointing to the same entity, especially in the case of multi-source data deduplication. Active learning trains the model by selecting the data items with the maximum information divergence and reduces the data to be annotated, which has unique advantages in dealing with big data annotations. However, most of the current active learning methods only employ classical entity matching and are rarely applied to data deduplication tasks. To fill this research gap, we propose a novel graph deep active learning framework for data deduplication, which is based on similarity algorithms combined with the bidirectional encoder representations from transformers (BERT) model to extract the deep similarity features of multi-source data records, and first introduce the graph active learning strategy to build a clean graph to filter the data that needs to be labeled, which is used to delete the duplicate data that retain the most information. Experimental results on real-world datasets demonstrate that the proposed method outperforms state-of-the-art active learning models on data deduplication tasks.

With the continuing development of the aquaculture industry, the stress associated with many environmental factors has severely restricted the growth of fish, reduced fish resistance to disease, and had a large negative impact on fishery production. Therefore, it is of great importance for the sustainable development of aquaculture to cultivate new fish varieties with strong stress resistance. Traditional hybridization and gynogenesis, selective breeding, modern breeding techniques such as molecular marker-assisted breeding and whole genome selection breeding can be used to develop efficient and accurate fish breeding strategies, and to cultivate new fish varieties with high stress resistance. This paper reviews the status of research on fish breeding for disease resistance, cold resistance, high temperature tolerance, hypoxia tolerance, salt tolerance, saline-alkali tolerance as well as non-specific stress resistance traits, analyzes trends in research on fish breeding for stress tolerance, and explores future development directions. Furthermore, this paper proposes new ideas for fish seed industry innovation to promote its continuous and sustainable development.

Abstract Background Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient’s prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases. Case presentation These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time. Conclusions The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Abstract The complicated geological environment of deep rocks poses new challenges to tunnel and mining engineering. Some thorny disasters such as large deformation of soft rock and rockburst are becoming more and more prominent. However, the classic tunnelling methods represented by the mine tunnelling method and the new Austrian tunnelling method are generally unsatisfactory in addressing these issues due to the limited self-stability of surrounding rock mass. Therefore, the excavation compensation method (ECM) with the core of active stress compensation has been proposed and applied in practical engineering construction to solve the above problems. After extensive engineering practice, the theoretical foundation, key technologies, and construction system of ECM have been established and improved. This article provides a comprehensive overview of this novel tunnelling method. In addition, its controlling effects on surrounding rock are demonstrated by two typical engineering examples. It could provide some new ideas and references for the development of future tunnelling technology.

Abstract Background Trigger thumb is a prevalent hand condition observed in children, and its management remains a topic of considerable debate, ranging from mere observation to surgical intervention. In recent times, there has been a growing interest in exploring nonoperative treatments as alternatives to surgical procedures for managing pediatric trigger thumb. Gaining insight into the prevalence of spontaneous resolution in pediatric trigger thumb is of paramount importance. However, the literature presents a wide variation in estimates regarding the prevalence of this spontaneous resolution, highlighting the need for further investigation and consensus. The aim of this review was to estimate the overall prevalence of spontaneous resolution among pediatric trigger thumb. Methods This study meticulously followed the PRISMA guidelines and registered in the PROSPERO. The PubMed, Embase, and Cochrane Library databases were searched for all relevant studies up to May 2024.Inclusion criteria were studies reported only observation spontaneous resolution pediatric trigger thumb, aged up to 14 years, reported at least 10 thumbs and followed up time at least 3 months. Confounded intervention treatment measure studies were excluded. To synthesize the prevalence rates from individual studies, we employed a random-effects meta-analysis. In order to uncover the sources of heterogeneity and to compare prevalence estimates across different groups, we performed sensitivity and subgroup analyses. To meticulously evaluate the quality of the included studies, the Joanna Briggs Institute’s quality assessment checklist was employed. Furthermore, to assess the heterogeneity among the studies, both Cochran’s Q test and the I² statistic were utilized. Results A total of eleven studies were included for the final analysis, with 599 pediatric trigger thumbs. Our final meta-analysis showed that more than one-third of these pediatric trigger thumb cases resolved spontaneously, with a resolution rate of 43.5% (95% CI 29.6–58.6). Subgroup analyses showed that in terms of age at the first visit, the prevalence of spontaneous resolution in the less than 24 months group and in the 24 months or older group was 38.7%(95% CI 18.1–64.4)and 45.8%(95% CI 27.4–65.4), respectively. There was no significant difference between the two groups(P = 0.690). When analyzing follow up time, the prevalence of spontaneous resolution in the 24 months or longer group and in the less than 24 months group was 58.9%(95% CI 41.6–74.2)and 26.8%(95% CI 14.7–43.8), respectively.There was significant statistical differences between the two groups(P = 0.009). Based on the initial severity of interphalangeal (IP) joint flexion contracture, the prevalence of spontaneous resolution in the 30 degrees or less group and in the other measurements group was 54.1%(95% CI 31.5–75.1)and 37.1%(95% CI 21.9–55.4), respectively.There was no significant difference between the two groups(P = 0.259). Conclusion Our study demonstrates that a significant proportion of pediatric trigger thumbs resolve spontaneously. This finding highlights the benefits of early observation in managing this condition. By prioritizing non-operative observation, both parents and surgeons are better equipped to make informed decisions regarding the treatment of pediatric trigger thumb, potentially reducing the need for surgical intervention.

Abstract While the anaerobic-anoxic-oxic (AAO) process is the most widely applied biological wastewater treatment process in municipal wastewater treatment plants (WWTPs), it struggles to meet the increasing demands on biological toxicity control of the treated effluent. To tackle this challenge, this study develops machine learning (ML)-based models for optimizing the AAO treatment process towards improving its toxicity reduction efficacy for the effluent. The water quality parameters, treatment process parameters, and biological toxicity information (based on the nematode bioassay) of the effluent collected from 122 WWTPs in China are used to train the models. The validated models accurately predict the effluent’s quality parameters (average R2 = 0.81) and the biological toxicity reduction ratio of treatment process (R2 = 0.86). To further improve the toxicity reduction, we developed a multiple objective optimization framework to optimize the AAO process via unit process recombination. In the short-range unit combination, the toxicity reduction ratio of the four-unit combined processes (up to 79.8% of anaerobic-aerobic-anaerobic-aerobic) is significantly higher than others. After optimization, it helps to improve the average toxicity reduction efficacy of 122 WWTPs from 48.6% to 70.7%, with a maximum of 87.5%. The methodologies and findings derived from this work are expected to provide the foundation for the optimization, expansion, and technical transformation of biological wastewater treatment in WWTPs.

Abstract The recent experimental confirmation of perovskite monolayers has sparked ongoing efforts in their prediction and synthesis, showcasing their flexible tunable band gap and potential in advanced functional devices. Although large-scale computational designs have been successfully performed for inorganic perovskite monolayers, the complexity introduced by organic cations hinders the same approaches applied to the hybrid halide perovskite monolayers. To address this challenge, we have proposed a high-throughput first-principles computational workflow that automates the design of hybrid halide perovskite monolayers. We strategically reduce the complexity of the configurations by analyzing the orientation of cations and the structural symmetry. Over 400 hybrid halide perovskite monolayers have been designed, and their structures and fundamental properties are stored in the database. Correlation analyses show a strong correlation between band gaps and metal-halogen-metal bond angles or metal-halogen bond lengths, consistent with prior studies for bulk and layered perovskites. The underlying physics that the band gap is modulated by the antibonding in the metal-halogen bond makes band gap engineering of hybrid halide perovskite monolayers feasible. Accordingly, initial research on lateral heterojunctions and solar cells has been conducted to explore the potential practical applications of the designed hybrid halide perovskite monolayers. Our study lays the foundation for further exploration of hybrid halide perovskite monolayers and highlights promising opportunities for their potential applications in electronic and optical devices.

Abstract Background Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology. Methods The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry. Results FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA. Conclusions FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion.

Abstract Younger generations are receiving their first regular digital device access at progressively earlier ages than previous generations on average, whereas disparities in their early digital device access are still being observed globally. The inequality of first regular digital device access may have profound long-term effects on one’s information and communication technology (ICT) skills, but no evidence has suggested how unequal first regular digital device access impacts one’s digital reading, which enables one to process and comprehend information in this digitized world. Thus, the current study investigated the relationship between the age at which children first regularly access digital devices and their digital reading performance at age 15 while considering the potential mediating effect of cognitive flexibility. A multilevel mediation model was proposed and tested using data from a cross-national sample of 156,277 15-year-old students from 18 OECD countries from the Programme for International Student Assessment (PISA). The results suggested that first regular digital device access after age 9 exerted a negative influence on digital reading scores in countries that generally had high levels of early digital access, and after age 13 in countries that had lower levels of early digital access. Additionally, cognitive flexibility mediated the association between the age at first regularly accessing digital devices and digital reading performance. Starting using digital devices regularly only after age 6, more evident at ages 9 to 12, was associated with lower levels of cognitive flexibility, which in turn led to worse digital reading performance. These findings demonstrated the importance of early first regular access to digital devices before school age (age 6) and highlighted the need for the cultivation of cognitive flexibility in family and school uses of digital devices.

PurposeTo assess the dosimetric effectiveness of image-guided radiation treatment (IGRT) and online adaptive radiation therapy (oART) for cervical cancer. As well as survival follow-up was conducted to validated the safety and efficacy of oART.MethodsA total of 15 cervical cancer patients were enrolled. oART was performed on a CT-integrated linear accelerator. The initial plan was revised to include the distribution of IGRT dose using daily fan-beam CT (FBCT) images, after which the distinctions between ART and IGRT in terms of target coverage and organs at risk (OARs) sparing were analyzed. Survival follow-up was conducted to validated the safety and efficacy of oART in this group.ResultsPTV Dmax value decreased by 1.23 Gy in the ART plan when compared to that in the IGRT plan; PTV D95 increased by 1.34 Gy; PTV V50 coverage increased by 4.86%; CTV coverage increased by 3.02%; PTV D2cc of the colon, rectum, and small intestine decreased by 1.24 Gy, 1.29 Gy, and 1.12 Gy, respectively. The V10 and V30 of the pelvis increased by 1.27% and 0.56%, respectively, while the V30 of the left and right femoral heads dropped by 2.82% and 3.41%, respectively. Except for the pelvic changes, all other differences were statistically significant (p < 0.01). The average time for the ART procedure was 21.22 min (range: 18.72–24.90 min). The median follow-up time is 28.0 months. Median event-free survival and overall survival were not reached. EFS rate and OS rate at 3 years were 79.4% and 92.9%.ConclusionOnline ART for cervical cancer can minimize the dose of OARs and enhance the target volume coverage significantly when compared to IGRT with satisfied survival time.

Purpose To study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary care since 2020. This cohort provides valuable data for researchers and policy-makers focused on diabetes management and public health strategies.Participants Diabetes was defined as having inpatient or outpatient encounters with a diagnosis of diabetes International Classification of Diseases-9/10 codes, any use of insulin or oral hypoglycaemic drugs, or one encounter with haemoglobin A1C >4.8 mmol/mol or 6.5%. Patients with diabetes have been continuously enrolled on hospitals and primary care in Nanjing since 2020. Demographic, medications and comorbidities data were extracted from clinical notes, diagnostic codes, labs, prescriptions and vital signs among different types of diabetes.Findings to date The NDC consisted of 1 033 904 patients from 1 January 2020 to 31 December 2022, the majority were male (50.62%) and from the Gulou district (30.79%). The clinical characteristics and medication usage of patients with type 1 diabetes, type 2 diabetes, gestational diabetes and other diabetes were assessed. The prevalences of hypertension, ischemic heart disease, and cerebrovascular disease were 49.72%, 17.85% and 24.90%, respectively.Future plans NDC will annually enrol eligible patients and include socioeconomic data in future updates. The data of NDC are maintained by the Department of Medical Informatics at Nanjing Medical University.

IntroductionTo establish a high myopia model in C57BL/6J mice with monocular form deprivation myopia (FDM) and investigate its ocular structure pathological trajectory.MethodsHealthy 3-week-old C57BL/6J mice were divided into an FDM group (n = 36) and a control group (n = 24). The left eyes of the FDM group were patched, while the right eyes served as controls. Biometric parameters and fundus morphology were assessed at baseline and after 4, 8, and 12 weeks of form deprivation.ResultsSignificant differences were observed in the deprived eyes, including longer axial length, higher refractive power, deeper vitreous chambers, thinner retina, choroid, and sclera, and smaller scleral fibers’ diameters under a transmission electron microscope. Retinal vascular area proportion in covered eyes decreased significantly (P < 0.05), with a decline rate of 11% from weeks 4 to 8 and a faster decline of 19% from weeks 8 to 12, while this proportion increased significantly in control eyes.DiscussionThis study successfully induced a high myopia model in mice with long-term form deprivation. The axial length grew dramatically in FDM in the first 8 weeks, while the pathological progress of the fundus accelerated from weeks 8 to 12.

ObjectiveAn UPLC-MS/MS method was developed and validated for simultaneous determination of atracurium (ATC), dexmedetomidine (DEX), midazolam (MDZ) and 1-hydroxymidazolam (1-OH-MDZ) and the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were investigated.MethodsThe analytes were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a mobile phase of acetonitrile-0.1% formic acid and a gradient mode. In the positive ion mode, the following mass transition pairs were monitored by multiple reaction monitoring (MRM) for the four analytes and IS: m/z 385.1→206.2 for ATC, m/z 201.2→95.1 for DEX, m/z 326.1→291.1 for MDZ, m/z 341.9→324.0 for 1-OH-MDZ, and 284.9→153.9 for diazepam (IS). Seven male patients undergoing aortic dissection surgery received general anesthesia and intravenous administration of ATC, DEX, and MDZ during the surgery. Venous blood was collected at different time points at the end of surgery and after surgery. The concentrations of ATC, DEX, MDZ, and 1-OH-MDZ were detected, and the pharmacokinetic parameters were calculated.ResultsThe method showed good linearity for each analyte. The inter-batch precision ranged from 1.37% to 9.87% and the intra-batch precision ranged from 2.41% to 10.72%; the accuracy ranged from 94.33% to 104.51%. Finally, the matrix effect, extraction recovery and stability data met the FDA recommended acceptance criteria for validation of bioanalytical methods. The t1/2 of ATC, DEX, MDZ and 1-OH-MDZ was (6.74 ± 2.27) h, (9.55 ± 4.93) h, (10.17 ± 5.35) h, and (6.90 ± 2.38) h, the Cmax, of ATC, DEX, MDZ and 1-OH-MDZ was (1054.20 ± 202.37) ng/mL, (1.93 ± 1.07) ng/mL, (1256.57 ± 389.09) ng/mL, and (1034.39 ± 292.92) ng/mL in patients undergoing aortic dissection surgery, respectively.ConclusionThe developed UPLC-MS/MS method for simultaneous determination of ATC, DEX, MDZ and 1-OH-MDZ in patient plasma was accurate, reproducible, specific. After continuous administration of ATC, DEX, and MDZ to patients undergoing surgery for acute aortic dissection, the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were studied.

Abstract Gliomas are highly heterogenous diseases with poor prognosis. Precise survival prediction could benefit further clinical decision‐making, clinical trial incursion, and health economics. Recent research has emphasized the prognostic value of magnetic resonance imaging, pathological specimens, and circulating biomarkers. However, the integrative potential and efficacy of these modalities require to be further validated. After incorporating 218 patients of The Cancer Genome Atlas glioma datasets of and 54 patients of the Huashan cohort with complementary prognostic information, we established a squeeze‐and‐excitation deep learning feature extractor for T1‐contrast enhanced images and histological slides and explored to screen significant circulating 5‐hydroxymethylcytosines (5hmC) profiles for glioma survival by least absolute shrinkage and selection operator‐Cox regression. Therefore, a prognostication predictive model with high efficiency was obtained through survival support vector machine multimodal integration of radiologic imaging, histopathologic imaging features, genome‐wide 5hmC in circulating cell‐free DNA and clinical variables, suggesting a valid strategy (concordance‐index = 0.897; Brier score = 0.118) for improved survival risk stratification of glioma patients.

Abstract Carbon dots (CDs)‐based zero‐dimensional nanomaterials with dimensions ranging from 1 to 10 nm have shown tremendous potential in the application of regenerative medicine, because of their unique physicochemical properties and favorable attributes like good biocompatibility, unique biological functions, low cost and high stability. These newly synthesized CDs‐based nanomaterials could replace traditional semiconductor quantum dots, which have obvious toxicity drawbacks and higher costs. CDs not only show sustained fluorescent quality and biocompatibility, but also serve as superior carriers for drug delivery, as well as for bioimaging‐guided detection of cells, drugs, and growth factors. So, they have been shown to play a role in various fields such as chemical and biological sensing, bioimaging, drug delivery, and photocatalysis. Thus, they are considered potential candidates for regenerative medicine applications. In this review, we provide a comprehensive summary of the classification of CDs, focusing on their formation mechanisms, micro‐/nanostructures, and distinctive properties. We describe their properties and synthesis methods in detail. Furthermore, we systematically highlight recent remarkable advances in the applications of CDs in regenerative medicine, such as bone and cartilage repair, wound healing, nerve regeneration, and myocardial regeneration, are systematically highlighted. Finally, we discuss the key challenges that lie ahead, outline future research directions, and explore the prospects of CDs‐based materials in regenerative medicine.

Abstract Background Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk.

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

Summary: The traditional parameter adjustment design makes it difficult to effectively regulate the acoustic insulation performance of periodic sandwich structures while meeting the lightweight and mechanical stiffness requirements. A dynamic three-field floating projection topology optimization (FPTO) method for periodic structures is proposed to meet the optimization requirements of low-noise and high-stiffness performance of lightweight periodic sandwich structures. The sound transmission loss is taken as the optimization objective, and the lightweight volume and mechanical stiffness performance are taken as the multiple constraints. The results show that a smooth topology configuration with superior sound insulation performance, high stiffness, and a freely customizable number of periodic cores can be obtained via the proposed method. The accuracy and effectiveness of the presented method are verified via 3D printing technology and impedance tube sound insulation experiments, providing an important reference for the optimal design of lightweight composite structures for vibration and noise reduction in transportation equipment.

This study delves into the paradox of the financial resource curse, exploring how the abundance of natural resources in a country paradoxically constrains firms' accessibility to financing. Despite the potential economic boon natural resources represent, evidence suggests that they can lead to less diversified economies, making it challenging for firms outside the resource sector to access financing. Our research aims to dissect this phenomenon by analyzing microeconomic statistics on the financial accessibility of enterprises, juxtaposed with macroeconomic statistics across 170 countries, encompassing over 10,000 firms surveyed from 1990 to 2022. The panel regression analysis allows us to control for both time-invariant country characteristics and global economic trends, providing insights into the causal relationship between resource dependence and financial access for firms. The results are striking, revealing that, indeed, countries with significant natural resource wealth tend to exhibit reduced financial accessibility for firms outside the resource extraction sector. The panel regression models indicate a robust negative correlation between the extent of a country's resource wealth and the ease with which non-resource firms can access financial capital. This suggests that the financial resource curse is not only a real phenomenon but also one that has significant implications for economic diversification and sustainable development. Moreover, findings underscore the need for targeted policy interventions. Countries with abundant natural resources should implement strategies that foster economic diversification, enhance the financial infrastructure to support a broader range of industries, and encourage the development of financial instruments tailored to the needs of non-resource sectors.

Abstract Carbon reduction is an important issue of global concern today, and with the construction industry accounting for a significant portion of global carbon emissions, carbon reduction research for the civil engineering industry is becoming increasingly important. The current research on carbon emission of buildings mainly focus on energy consumption, choice of building materials, and energy‐saving technologies. While different construction programs can affect the construction sequence and have a significant impact on carbon emissions, especially for ultra‐high‐rise steel structures. In this paper, carbon emission is introduced as the optimization objective, and a nodal optimization procedure based on carbon emission is given to explore the optimization scheme of ultra‐high‐rise steel structure construction based on carbon emission. Calculations using the carbon emission factor method were carried out to analyze the differences in carbon emissions between different construction schemes and to explore the impact of the method of carbon emission optimization. Results show that the combined lifting scheme can save 463.4 kg carbon emissions and reduce the number of lifts by 780 times.

ABSTRACT: Slightly acidic electrolyzed water (SAEW) is a safe and effective disinfectant, but its sterilizing efficiency is compromised by organic matter on the egg surface. Electrolyzed reduced water (ERW) is a harmless cleaner with a decontamination effect on a variety of surfaces and can be used to remove organic matter. This study assesses the effectiveness of a combination of ERW and SAEW in eliminating Salmonella and manure mixture from egg surfaces, as well as its impact on egg quality during storage. The results show that ERW (74.14%) was more effective than deionized water (DW, 64.69%) and SAEW (70.20%) (P < 0.05) in removing manure from egg surfaces. The damage to the cuticle of eggshell treated with ERW for 28 s was similar to that of DW (P > 0.05) and less than that of SAEW (P < 0.05). Spraying ERW for 10 s followed by SAEW for 18 s (ERW + SAEW) completely removed Salmonella from the egg surface, with no bacteria detected in the residual wash solution. Additionally, ERW + SAEW demonstrated superior preservation of egg quality during storage at 25℃ than the control and ERW single treatment (P < 0.05). Moreover, ERW + SAEW resulted in less weight loss compared to SAEW single treatment (P < 0.05). In conclusion, the sequential use of ERW and SAEW appears to be a promising approach for sterilizing eggs. It not only removes organic matter and Salmonella from the egg surface but also improves the preservation quality of the egg at 25 ℃.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

The escalating levels of atmospheric CO2, primarily attributed to human activities, underscore the urgent need for innovative solutions to mitigate environmental challenges. This study delves into the electrochemical reduction of CO2 as a promising avenue for sustainable carbon capture and utilization. Focused on the formation of formate (HCOO−/HCOOH), a high-value product, the research explores the integration of nonthermal plasma (NTP) with electrochemical processes—an approach rarely studied in existing literature. A comprehensive investigation involves varying parameters such as plasma discharging voltage, carrier gas, discharging mode, electrolysis voltage, polarity, and plasma type. The electrochemical tests employ a 10 wt.% Pd/C catalyst, and formate production is quantitatively analyzed using NMR. Results reveal that NTP significantly enhances CO2 reduction, with key factors influencing formate yield elucidated. The study reveals the complexity of CO2 electrochemical reduction, providing novel insights into the synergistic effects of NTP. These findings contribute to advancing sustainable technologies for CO2 utilization, paving the way for more efficient and environmentally friendly processes in the pursuit of a carbon-neutral future.

Abstract Background Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. Methods We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE−/−) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay. Results miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs. Conclusion These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.

Abstract Background In recent years, gene clustering analysis has become a widely used tool for studying gene functions, efficiently categorizing genes with similar expression patterns to aid in identifying gene functions. Caenorhabditis elegans is commonly used in embryonic research due to its consistent cell lineage from fertilized egg to adulthood. Biologists use 4D confocal imaging to observe gene expression dynamics at the single-cell level. However, on one hand, the observed tree-shaped time-series datasets have characteristics such as non-pairwise data points between different individuals. On the other hand, the influence of cell type heterogeneity should also be considered during clustering, aiming to obtain more biologically significant clustering results. Results A biclustering model is proposed for tree-shaped single-cell gene expression data of Caenorhabditis elegans. Detailedly, a tree-shaped piecewise polynomial function is first employed to fit non-pairwise gene expression time series data. Then, four factors are considered in the objective function, including Pearson correlation coefficients capturing gene correlations, p-values from the Kolmogorov-Smirnov test measuring the similarity between cells, as well as gene expression size and bicluster overlapping size. After that, Genetic Algorithm is utilized to optimize the function. Conclusion The results on the small-scale dataset analysis validate the feasibility and effectiveness of our model and are superior to existing classical biclustering models. Besides, gene enrichment analysis is employed to assess the results on the complete real dataset analysis, confirming that the discovered biclustering results hold significant biological relevance.

In this paper, we consider the evolution of a new probability distribution called the exponential flexible Weibull distribution. The proposed exponential flexible Weibull distribution is obtained by combining the flexible Weibull extension with the exponential T-X strategy. For the exponential flexible Weibull, the estimators of the model parameters are derived mathematically. The appraisal of these parameters is accomplished through a simulation study. The applicability and virtuoso of the exponential flexible Weibull distribution are exemplified via two data sets. Furthermore, we implement the state-of-the-art deep learning algorithms, specifically Artificial Neural Networks and Extreme Gradient Boosting, which are widely employed in real-world applications. A comprehensive comparative analysis is conducted to assess the relative performance of these methodologies.

Chemical inhibition is one of the important measures for the prevention and control of coal spontaneous combustion. This paper proposed a quasi-ionic liquid inhibition method based on deep eutectic solvents (DES). First, seven kinds of room temperature deep eutectic solvents were prepared and screened using a heating method. The changes in the functional groups and thermodynamic characteristics of different DES-treated coal samples were analyzed. On this basis, the density functional theory was utilized to analyze the differences in the modification of coal's physicochemical properties by the hydrogen bond strength in the DES, and the inhibition mechanism of deep eutectic solvents and their optimal hydrogen bond strength were deduced. The results showed that after the DES treatment, the hydrogen bond network in coal was disrupted and rearranged. The relative abundance of aliphatic and aromatic hydrocarbons increased by 10%−37%, the content of aliphatic side chains decreased by 9.38%−20.65%, the relative abundance of oxygen-containing functional groups (C=O and C—O) decreased by 22.88%−56.94%, and free low-molecular compound and minerals were leached out. After the DES treatment, the mass loss during the evaporation and desorption stage of coal and the oxygen uptake during the oxygen absorption stage decreased. The heat release during the low temperature oxidation stage and the thermal decomposition stage was reduced by 8.94%−77.51% and 5.40%−26.20%, respectively. The stronger the electronegativity of the hydrogen bond acceptor site in the HBA, the greater the hydrogen bond strength formed between HBA and HBD. The hydrogen bond strength in the DES was positively correlated with the degree of destruction of the hydrogen bond network in coal, and was locally correlated with the oxygen uptake during the oxygen absorption stage, the heat release during low temperature oxidation, and the mineral removal rate. The DES weakened the low-temperature oxidation reactivity of coal by dissolving its active components, and increased the bond dissociation enthalpy of coal by promoting the rearrangement of hydrogen bonds into more thermally stable [OH]4 and OH—N hydrogen bonds. However, the excessive strong hydrogen bond strength would inhibit the removal and dissolution of active side chains. Therefore, the hydrogen bond strength of deep eutectic solvents used to inhibit coal spontaneous combustion should be controlled between 69.45 kJ/mol and 160.00 kJ/mol.

Abstract Motivation Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. Results In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS . Scientific contribution First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy.

Planar sliding is one of the frequently observed types of failure in rock slopes. Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses. The accuracy of planar sliding kinematic analysis is significantly influenced by the value assigned to the lateral limit angle γlim. However, the assignment of γlim is currently used generally based on an empirical criterion. This study aims to propose an approach for determining the value of γlim in deterministic and probabilistic kinematic planar sliding analysis. A new perspective is presented to reveal that γlim essentially influences the probability of forming a potential planar sliding block. The procedure to calculate this probability is introduced using the block theory method. It is found that the probability is correlated with the number of discontinuity sets presented in rock masses. Thus, different values of γlim for rock masses with different sets of discontinuities are recommended in both probabilistic and deterministic planar sliding kinematic analyses; whereas a fixed value of γlim is commonly assigned to different types of rock masses in traditional method. Finally, an engineering case was used to compare the proposed and traditional kinematic analysis methods. The error rates of the traditional method vary from 45% to 119%, while that of the proposed method ranges between 1% and 17%. Therefore, it is likely that the proposed method is superior to the traditional one.

Abstract The relationship between oxygen sensing and autophagy in human sperms was explored in this study. Health semen and asthenozoospermia (astheno) semen were incubated with hypoxia-inducible factor-1α (HIF-1α) interferents, i.e., lificiguat (YC-1) or cobalt chloride (CoCl2), respectively. Label-free quantitative proteomic technology was used to identify the differentially expressed proteins in human semen under the hypoxia condition. Selected proteins were detected with ELISA. It was found that the autophagy levels of sperm in the YC-1 + health group or CoCl2 + astheno group increased while the vitality decreased. A total of 17, 34 and 35 differentially expressed proteins were observed in the Astheno group, the YC-1 + health group and the CoCl2 + astheno group, respectively. These proteins were primarily associated with protein processing in endoplasmic reticulum, Th17 cell differentiation, progesterone-mediated oocyte maturation, glycolysis/gluconeogenesis, HIF-1 signaling pathway, biosynthesis of amino acids, and carbon metabolism. The expression levels of protein HIF-1α, LC3B, histone H4, cathepsin L and ENO1 changed significantly in the groups. The study suggests that hypoxia can increase sperm autophagy level and reduce their vitality through HIF-1 signaling pathway and glycolysis/gluconeogenesis signaling pathway. Furthermore, proteins histone H4, cathepsin L, glutathione synthetase and ENO1 are proposed as potential biomarkers of autophagy and vitality in asthenozoospermia sperm.

Ratoon rice, which refers to a second harvest of rice obtained from the regenerated tillers originating from the stubble of the first harvested crop, plays an important role in both food security and agroecology while requiring minimal agricultural inputs. However, accurately identifying ratoon rice crops is challenging due to the similarity of its spectral features with other rice cropping systems (e.g., double rice). Moreover, images with a high spatiotemporal resolution are essential since ratoon rice is generally cultivated in fragmented croplands within regions that frequently exhibit cloudy and rainy weather. In this study, taking Qichun County in Hubei Province, China as an example, we developed a new phenology-based ratoon rice vegetation index (PRVI) for the purpose of ratoon rice mapping at a 30 m spatial resolution using a robust time series generated from Harmonized Landsat and Sentinel-2 (HLS) images. The PRVI that incorporated the red, near-infrared, and shortwave infrared 1 bands was developed based on the analysis of spectro-phenological separability and feature selection. Based on actual field samples, the performance of the PRVI for ratoon rice mapping was carefully evaluated by comparing it to several vegetation indices, including normalized difference vegetation index (NDVI), enhanced vegetation index (EVI) and land surface water index (LSWI). The results suggested that the PRVI could sufficiently capture the specific characteristics of ratoon rice, leading to a favorable separability between ratoon rice and other land cover types. Furthermore, the PRVI showed the best performance for identifying ratoon rice in the phenological phases characterized by grain filling and harvesting to tillering of the ratoon crop (GHS-TS2), indicating that only several images are required to obtain an accurate ratoon rice map. Finally, the PRVI performed better than NDVI, EVI, LSWI and their combination at the GHS-TS2 stages, with producer’s accuracy and user’s accuracy of 92.22 and 89.30%, respectively. These results demonstrate that the proposed PRVI based on HLS data can effectively identify ratoon rice in fragmented croplands at crucial phenological stages, which is promising for identifying the earliest timing of ratoon rice planting and can provide a fundamental dataset for crop management activities.

Abstract To improve the precision of defect categorization and localization in images, this paper proposes an approach for detecting surface defects in hot-rolled steel strips. The approach uses an improved YOLOv5 network model to overcome the issues of inadequate feature extraction capacity and suboptimal feature integration when identifying surface defects on steel strips. The proposed method achieves higher detection accuracy and localization precision, making it more competitive and applicable in real production. Firstly, the multi-scale feature fusion (MSF) strategy is utilized to fuse shallow and deep features effectively and enrich detailed information relevant to target defects. Secondly, the CSPLayer Res2Attention block (CRA block) residual module is introduced to reduce the loss of defect information during hierarchical transmission, thereby enhancing the extraction of fine-grained features and improving the perception of details and global features. Finally, the experimental results indicate that the mAP on the NEU-DET and GC10-DET datasets approaches 78.5% and 67.3%, respectively, which is 4.9% and 2.1% higher than that of the baseline. Meanwhile, it has higher precision and more precise localization capabilities than other methods. Furthermore, it also achieves 59.2% mAP on the APDDD dataset, indicating its potential for growth in further domains.

A novel meta steel with negative Poisson’s ratio effect (termed as micro-NPR steel) is developed for rock support in deep underground engineering. It possesses high strength, high ductility, and high energy absorption characteristics. In this paper, static tension and modified dynamic drop hammer tests are performed on this novel material to investigate its mechanical properties first. Then based on this material, a new generation of micro-NPR anchor cable is developed and applied in field tests subjected to blasting dynamic loads. The results of laboratory tests reveal that the ultimate elongation of micro-NPR steel under dynamic impacts is more than 30% and it is over 1.5 times that of Q235; the plastic and total energy absorption of micro-NPR are both significantly higher than that of Q235. Field test indicates the fine controlling effect of micro-NPR anchor cable on surrounding rock mass under dynamic loads. Axial force confirms that micro-NPR cables can distribute and absorb the dynamic energy uniformly around the supported rock when subjected to dynamic disturbance, avoiding local failure induced by excessive stress concentration. The excavation compensation principle and energy-absorbing characteristics are used to explain the support mechanisms. Thus, micro-NPR material and anchor cable can control and prevent dynamic disasters in deep underground engineering effectively.

Rockburst disasters occur frequently during deep underground excavation, yet traditional concepts and methods can hardly meet the requirements for support under high geo-stress conditions. Consequently, rockburst control remains challenging in the engineering field. In this study, the mechanism of excavation-induced rockburst was briefly described, and it was proposed to apply the excavation compensation method (ECM) to rockburst control. Moreover, a field test was carried out on the Qinling Water Conveyance Tunnel. The following beneficial findings were obtained: Excavation leads to changes in the engineering stress state of surrounding rock and results in the generation of excess energy ΔE, which is the fundamental cause of rockburst. The ECM, which aims to offset the deep excavation effect and lower the risk of rockburst, is an active support strategy based on high pre-stress compensation. The new negative Poisson’s ratio (NPR) bolt developed has the mechanical characteristics of high strength, high toughness, and impact resistance, serving as the material basis for the ECM. The field test results reveal that the ECM and the NPR bolt succeed in controlling rockburst disasters effectively. The research results are expected to provide guidance for rockburst support in deep underground projects such as Sichuan–Xizang Railway.

Abstract Background Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. Methods This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. Results (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. Conclusions Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Abstract Vitamin C played pleiotropic roles in critical illness and vitamin C insufficiency was predictive of the development of multiple organ failure. Currently, the prevalence of vitamin C insufficiency in Chinese critically ill patients is rarely determined and there are no established bedside tools to predict hypovitaminosis C. To develop a nomogram to identify patients with high risk of hypovitaminosis C, we performed a bi-center prospective cohort study at two ICUs of the first and sixth medical center in PLA General Hospital, Beijing, China from May 6th to July 31st, 2021 We identified 322 eligible patients. 62.4% patients were hypovitaminosis C. 7 features, including source of infection, the level of serum albumin, age, male gender, sepsis, vascular disease, and wasting of vitamin C by the kidney, were selected using LASSO algorithm and therefore included in the nomogram. In the testing set, our model showed moderate discrimination ability with areas under the curve of 0.75 [0.64–0.84]. Variable importance evaluated by SHAP value highlighted two novel important predictors, i.e., abdominal infection and the level of serum albumin. In conclusion, we first reported a high burden of vitamin C insufficiency in Chinese adult patient in the ICU. We also constructed a prediction model to timely identify patients with high risk of hypovitaminosis C, which allows the clinicians to choose appropriate candidates for Vitamin C repletion in clinical practice or clinical trials.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.